The invention relates to a process for the production of optically-active 4-amino-3-hydroxycarboxylic acids and their N-protected derivatives.
The products of the process according to the invention have the general formula: ##STR1## wherein R.sup.1 is an optionally branched and/or substituted alkyl group with 1 to 10 C atoms or an optionally substituted aryl, arylalkyl or cycloalkyl group and X is a hydrogen or an amino protective group. These compounds have two chiral centers and, therefore, can occur in 4 stereoisomeric forms each.
The process according to the invention allows production alternatively of the (3R,4R) or (3S,4S) enantiomer. These two enantiomers are comprised by the stereochemical designations (rel-3R,4R) or (3R*,4R*). The first of the two designations is used below.
Some of these compounds, especially those with R.sup.1 =isopropyl or cyclohexyl, are of interest as the structural element of peptides, which have enzyme inhibiting effects. But only the (3S,4S)-stereoisomer is effective in this connection. Especially (3S,4S)-4-amino-3-hydroxy-6-methylheptanoic acid, known by the trivial name statine, which is contained in the renin inhibitor pepstatine, already was the aim of numerous different synthesis processes [see, for example, European Patent No. 0210896; H. J. Altenbach. Nachr. Chem. Tech. Lab., 36, (1988), pages 756 to 758; M. Saiah et al., Tetrahedron Asymmetry, 2, (1991), pages 111 and 112, as well as literature cited there]. However, these syntheses are only poorly suitable or unsuitable for the economical production of large amounts of different substituted 4-amino-3-hydroxycarboxylic acids, because they require partly expensive starting materials, partly are suitable only on a laboratory scale and partly the necessary starting materials are available at all only for specific radicals R.sup.1 of general formula I.